Abstract：
BACKGROUND: Warfarin is widely used for the prevention and treatment of thrombotic events. This study aimed to examine the influence of gene polymorphisms on the early stage of warfarin therapy in patients following heart valve surgery.
METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed.
RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability.
CONCLUSIONS: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.
METHODS: Nine single nucleotide polymorphisms were genotyped using microarray chips, categorizing patients into three groups: normal responders (Group I), sensitive responders (Group II), and highly sensitive responders (Group III). The primary clinical outcomes examined were time in therapeutic range (TTR) and international normalized ratio (INR) variability. To investigate potential influencing factors, a generalized linear regression model was employed.
RESULTS: Among 734 patients, the prevalence of CYP2C9*3-1075A > C, CYP2C19*3-636G > A, and CYP2C19*17-806C > T variants were 11.2%, 9.9%, and 1.9% of patients, respectively. VKORC1-1639G > A or the linked -1173C > T variant was observed in 99.0% of the patients. Generalized linear model analysis revealed an impact of sensitivity grouping on INR variability. Compared to Group I, Group II showed higher TTR values (p = 0.023), while INR variability was poorer in Group II (p < 0.001) and Group III (p < 0.001). Individual gene analysis identified significant associations between CYP2C9*3-1075A > C (p < 0.001), VKORC1-1639G > A or the linked -1173 C > T (p = 0.009) and GGCX-3261G > A (p = 0.019) with INR variability.
CONCLUSIONS: The genotypes of CYP2C9, VKORC1, and GGCX were found to have a significant impact on INR variability during the initial phase of warfarin therapy. However, no significant association was observed between TTR and gene polymorphisms. These findings suggest that focusing on INR variability is crucial in clinical practice, and preoperative detection of gene polymorphisms should be considered to assist in the initiation of warfarin therapy.
摘要：
背景：华法林广泛用于预防和治疗血栓事件。本研究旨在研究基因多态性对心脏瓣膜手术后患者华法林治疗早期的影响。
方法：使用微阵列芯片对9个单核苷酸多态性进行基因分型，将患者分为三组：正常反应者(第一组)，敏感响应者(第二组)，和高度敏感的反应者（组III）。检查的主要临床结果是治疗范围内的时间（TTR）和国际标准化比率（INR）变异性。为了调查潜在的影响因素，采用广义线性回归模型。
结果：在734名患者中，CYP2C9*3-1075A的患病率>C，CYP2C19*3-636G>A,CYP2C19*17-806C>T变异体为11.2%，9.9%，1.9%的患者，分别。在99.0%的患者中观察到VKORC1-1639G>A或连接的-1173C>T变体。广义线性模型分析揭示了敏感性分组对INR变异性的影响。与第一组相比，II组显示出较高的TTR值（p=0.023），而INR变异性在II组(p<0.001)和III组(p<0.001)较差。个体基因分析确定了CYP2C9*3-1075A>C之间的显着关联（p<0.001），VKORC1-1639G>A或连接的-1173C>T（p=0.009）和GGCX-3261G>A（p=0.019），具有INR变异性。
结论：发现CYP2C9、VKORC1和GGCX的基因型在华法林治疗的初始阶段对INR变异性有显著影响。然而,TTR与基因多态性之间未观察到显著关联.这些发现表明，关注INR变异性在临床实践中至关重要。术前检测基因多态性应被考虑以协助开始华法林治疗。
方法：使用微阵列芯片对9个单核苷酸多态性进行基因分型，将患者分为三组：正常反应者(第一组)，敏感响应者(第二组)，和高度敏感的反应者（组III）。检查的主要临床结果是治疗范围内的时间（TTR）和国际标准化比率（INR）变异性。为了调查潜在的影响因素，采用广义线性回归模型。
结果：在734名患者中，CYP2C9*3-1075A的患病率>C，CYP2C19*3-636G>A,CYP2C19*17-806C>T变异体为11.2%，9.9%，1.9%的患者，分别。在99.0%的患者中观察到VKORC1-1639G>A或连接的-1173C>T变体。广义线性模型分析揭示了敏感性分组对INR变异性的影响。与第一组相比，II组显示出较高的TTR值（p=0.023），而INR变异性在II组(p<0.001)和III组(p<0.001)较差。个体基因分析确定了CYP2C9*3-1075A>C之间的显着关联（p<0.001），VKORC1-1639G>A或连接的-1173C>T（p=0.009）和GGCX-3261G>A（p=0.019），具有INR变异性。
结论：发现CYP2C9、VKORC1和GGCX的基因型在华法林治疗的初始阶段对INR变异性有显著影响。然而,TTR与基因多态性之间未观察到显著关联.这些发现表明，关注INR变异性在临床实践中至关重要。术前检测基因多态性应被考虑以协助开始华法林治疗。
